Lung disease is a significant cause of morbidity and mortality in the United States. While all other major causes of death are decreasing, age-adjusted mortality due to lung disease continues to rise. The overall purpose of this COBRE Phase III renewal application is to continue the development of the research program in Lung Biology and Disease at The Vermont Lung Center (VLC) of the University of Vermont College of Medicine. The keystone of the VLC program is excellence. The scientific strengths include airway epithelial cell biology, cystic fibrosis, asthma inflammation, lung physiology, translational animal studies, and clinical investigation into the pathogenesis of lung disease. In the last funding cycle we have continued to amass a record of productivity including: recruitment of a critical mass of well trained PhD and MD pulmonary scientists, high-impact peer-reviewed publications and continued as well as considerable increase in extramural funding. A critical requirement for the continued success of the Vermont Lung Center is the stimulating environment in which optimal career development can occur. The current goals of the VLC-COBRE are therefore to: 1) Develop the careers of a group of talented MD and PhD biomedical investigators 2) Provide skilled mentoring and consultation on com petitive scientific approaches 3) Maintain a cutting edge research milieu 4) Develop a clinical studies core, maintain transgenic/knockout animal and small animal phenotyping core, This proposed program will build towards sustainability of the VLC by forming the nexus from which center grant applications will be created. This proposal also addresses the urgent need to expand and support translational multidisciplinary research at UVM, because this is how advances in basic molecular, cellular and genetic science are converted into new methods of diagnosis and therapy.